Oral preparation

ABSTRACT

An aqueous oral preparation is provided which contains a peroxygen compound and a flavor which is stable in such system. The peroxygen compound is preferably hydrogen peroxide. The preparation may be in the form of a mouthrinse, a paste or a gel. Many optional ingredients may be included such as ethanol, polyhydric alcohols, non-ionic surfactants, fluorides, color, preservative, sweetener, and the like. A preferred rinse includes ethanol, sorbitol, a Pluronic surfactant, a Tween surfactant, sodium saccharin, and color. A typically preferred gel is similar to the rinse but contains about 20 wt. % of a thickener.

This application is a continuation-in-part of application Ser. No.455,388 filed Jan. 3, 1983, now U.S. Pat. No. 4,431,631.

This invention relates to an oral preparation and especially to aperoxide-containing aqueous mouthwash or mouthrinse solution, gel orpaste.

It has long been recognized in the art that hydrogen peroxide and otherperoxygen-containing agents are effective in curative and/orprophylactic treatments with respect to caries, dental plaque,gingivitis, periodontitis, mouth odor, tooth stains, recurrent aphthousulcers, denture irritations, orthodontic appliance lesions,postextraction and posperiodontal surgery, traumatic oral lesions andmucosal infections, herpetic stomatitis and the like.Peroxide-containing agents in the oral cavity exert a chemomechanicalaction generating thousands of tiny oxygen bubbles produced byinteraction with tissue and salivary enzymes. The swishing action of amouthrinse enhances this inherent chemomechanical action. Such actionhas been recommended for delivery of other agents into infected gingivalcrevices. Peroxide mouthrinses and other oral preparations preventcolonization and multiplication of anaerobic bacteria known to beassociated with peridontal disease. Peroxygen-containing gels or pastesare indicated and/or desirable where it is required to selectively treatareas for more than a few seconds, such gels and pastes tending toremain at the site of application for a time sufficient for the peroxideto manifest its maximum effectiveness.

It is however also known that most peroxy compounds such as hydrogenperoxide and metal peroxides such as magnesium peroxide in such oralcompositions, by interaction with other common excipients therein, tendto be unstable in storage, continuously losing the capacity to releaseactive or nascent oxygen over relatively short periods of time, and tendto diminish or destroy the desired function of such excipients. Amongsuch excipients are flavors and coloring agents added to enhance theacceptability of the preparations to those in need of an oralperoxidizing treatment. Numerous proposals have been made for solvingthe aforementioned problems, including encapsulating the peroxidecompound and/or the peroxide-sensitive excipient, using more stable butmore expensive peroxy compounds such as organic peroxides andperoxydiphosphate salts (e.g. the tetrapotassium salt), etc.

It is an object of this invention to provide oral preparation which willnot be subject to one or more of the aforementioned disadvantages anddeficiencies. Another object of this invention is the provision of afoaming oxygenating oral preparation in ready-to-use form having apleasant flavor and/or color and enhanced stability in storage. Stillanother object of this invention is the provision of a mouthrinse havinga basis of the readily available, highly effective and economicalhydrogen peroxide. Still another further object of this invention is theprovision of an oral oxygenating preparation in the form of a gel. Otherobjects and advantages will appear as the description proceeds.

The attainment of one or more of the above objects is made possible bythis invention which comprises:

an aqueous oral preparation containing, approximately by weight:

A. 1-3% of hydrogen peroxide, and

B. an effective flavoring amount of a flavor selected from the groupconsisting of

b1. wintergreen flavor containing methyl salicylate and menthol in aweight ratio of about 3:1 to 5:1, and

b2. a cinnamon flavor composition comprising about 6-9% menthol, 32-38%cinnamic aldehyde and 6-9% clove oil.

The aforementioned component "B" flavors have surprisingly been found tobe satisfactorily stable and compatible in the presence of hydrogenperoxide, in contrast to other flavors, e.g. fruity flavors such asorange, lemon and lime, and even minty flavors other than the aforesaidb1 component wintergreen flavor, such as peppermint and spearmint.Effective flavor amounts are as desired, typically ranging from about0.05 to 1.0%, preferably about 0.1 to 0.5%, by weight of the oralcomposition.

It is generally desirable, and often preferred to include numerousadjuvants to the basic compositions of this invention. These include (C)ethanol; (D) polyhydric alcohols such as glycerol and sorbitol; (E)surfactants, especially nonionics, and of these, those which have beenfound to have acceptable stability in the aqueous peroxygen environment;(F) a sweetener; (G) anti-caries agents; (H) thickeners; (I)preservatives; (J) coloring agents; and the like.

With references to the ethyl alcohol a convenient amount is 1 to 5% byweight based on the weight of the total composition, with 3-10% being apreferred range. The polyhydric alcohol (D) may range from about 1 to20% by weight, with 3-15% being preferred.

Sorbitol is preferred as the component D polyhydric alcohol sincealthough glycerin is sufficiently compatible with the other components,particularly the hydrogen peroxide, it interferes with at least onecommon method for analysis of the peroxide content. Component D servesas humectant, carrier (with the ethanol) and viscosity-control agent.

The component E surfactant, which is preferably non-ionic comprises, inthe more preferred embodiments, two general types of surfactants; thoseknown under the Tween and other trademarks and those block polymersavailable under the Pluronic trademarks. The former (Tween) surfactantsare mixtures of C₁₀₋₁₈ fatty acid esters of sorbitol (and sorbitolanhydrides), consisting predominantly of the monoester, condensed withabout 10-30, preferably about 20, moles of ethyleneoxide. The fatty acid(aliphatic hydrocarbyl monocarboxylic acid) may be saturated orunsaturated, e.g. lauric, palmitic, stearic, oleic acids. Polysorbate 20(e.g. Tween 20) is especially preferred, commonly referred to aspolyoxyethylene (20) sorbitan monolaurate. The Pluronic surfactants arestraight chain polymers containing a hydrophobic (water insoluble)polyoxypropylene moiety polyoxyethylenated at both ends with sufficientwater-solubilizing oxyethylene groups to achieve the desiredwater-solubility, HLB, (hydrophyliclipophylic balance) and dispersingsurfactant activity. The solid F series of Pluronics are preferred inwhich the molecular weight of the polyoxypropylene moiety ranges fromabout 950 to 4,000 and constitutes about 20-30% of the molecule (i.e.80-70% polyoxyethylene in the molecule). Pluronic F 108 is especiallypreferred, in which the said hydrophobic moiety has a molecular weightof about 3250 and constitutes about 2% of the molecule. This surfactanthas a molecular weight of about 14,000-16,000.

The surfactant components serve as solubilizing, dispersing,emulsifying, wetting and viscosity-control agents and when used incertain combinations, are especially effective to solubilize the flavor.

A particularly useful combination of surfactants is one where at leastone surfactant is of the Pluronic type and at least one is of thepolysorbate type.

For the aforementioned functions of solubilizing, dispersing,emulsifying, wetting and viscosity-control, it is preferred to use fromabout 0.1% to about 10% by weight of surfactant; more preferred range isabout 0.2% to about 6% and a most preferred range is from about 0.5 toabout 5%.

Where combination of Pluronic and Polysorbate surfactants are used theymay be employed in weight ratios of from about 20:1 to about 1:10 andpreferably from about 10:1 to about 1:5.

As described above the compositions of this invention may contain otherfunctional agents such as anticaries agents and the like.Fluorine-providing anticaries compounds optionally present in thesesolutions may be partially or fully water-soluble. They arecharacterized by their ability to release fluorine-containing ions inwater and by substantial freedom from reaction with other compounds ofthe oral preparation. Among these materials are inorganic fluoridesalts, such as soluble alkali metal, alkaline earth metal and heavymetal salts, for example, sodium fluoride, potassium fluoride, ammoniumfluoride, calcium fluoride, a copper fluoride such as cuprous fluoride,zinc fluoride, a tin fluoride such as stannic fluoride or stannouschlorofluoride, barium fluoride, sodium fluorosilicate, ammoniumfluorosilicate, sodium fluorozirconate, sodium monofluorophosphate,aluminum mono- and di-fluorophosphate, and fluorinated sodium calciumpyrophosphate. Alkali metal and tin fluorides, such as sodium andstannous fluorides, sodium monofluorophosphate (MFP) and mixturesthereof, are preferred.

The amount of the fluorine-providing compound is dependent to someextent upon the type of compound, its solubility, and the type of oralpreparation, but it must be a nontoxic amount. An amount of suchcompound which releases a maximum of about 1% of fluoride ion by weightof the preparation is considered satisfactory. Any suitable minimumamount of such compound may be used, but it is preferable to employsufficient compound to release about 0.005 to 1%, and preferably about0.1% of fluoride ion. Typically, especially in the cases of MFP, alkalimetal fluorides and stannous fluoride, this component is optionallypresent in these compositions in an amount of about 0.01 to 2 wt. %,preferably about 0.05 to 1 wt. %, especially about 0.76 wt. %.

A coloring agent is also often desirable for enhanced appearance andacceptability, but should be carefully selected for compatibility withthe other named components, particularly the hydrogen peroxide. Greencoloring agents for example have been generally found to be unacceptablein this regard. FD & C Blue No. 1 and Red No. 40 have been found tosatisfy the requirements of this invention, employed in effectivecoloring amounts as desired, typically in concentrations of about 0.0002to 0.004% by weight in the solution.

A preferred component F sweetener compound is saccharin, especiallysodium saccharin, but other known orally acceptable sweetener compoundsmay be employed, typically in concentrations of about 0.01 to 5 wt. %,such as xylitol, sodium cyclamate, perillartine, D-tryptophan,aspartame, dihydrochalcones and the like.

One preferred form of the oral compositions of this invention is assolutions in an aqueous and preferably an aqueous-ethyl alcohol carrier.A typical mode of preparation involves judiciously mixing the selectedcomponents for proper solubilization in the carrier medium (e.g.ethanol/polyhydric alcohol/water), any coloring agent and hydrogenperoxide in order being preferably added after any of the other selectedcomponents.

As pointed out above one may incorporate into the oral compositions ofthis invention any of the conventional preservatives (e.g. in weightamounts of from about 0.0000% to about 5% and preferably about 0.01% toabout 1%) which are pharmaceutically acceptable.

Further one may formulate the compositions as gels or pastes utilizing,preferably peroxide-stable thickening and gelling agents. Useable agentsinclude xanthan gum, guar gum, locust gum, carboxylic interpolymers asdisclosed in U.S. Pat. No. 2,798,053, Pluronic Polyols particularly ofthe "10" and "12" Series and of these especially the solid products witha hydrophobe of M.W. of about 3500 to 4000 and with from 30 to 80%hydrophilic polyoxyethylene groups. Examples of such Pluronic compoundsare P103, P104, P105, P123, F108 and F127. The most preferred gellingagent is Pluronic F127. The amount of thickener or gelling agent mayvary widely. As little as 1 or 2 or 3 or 4 or 5% may suffice for someapplications whereas for most gels a most representative range would be5 to 50% with 10 to 30 preferred and 15 to 25 most preferred.

The pH of the solutions and other pastes and gels of this inventiongenerally ranges from about 4 to 7, and preferably about 5. Generally,the pH may be from 6 to 7 when the composition is first prepared andthen slowly drop to an equilibrium pH of from about 4 to about 6.

The following examples of preferred embodiments of this invention areonly illustrative. All amounts and proportions referred to herein and inthe appended claims are by weight unless otherwise indicated. Typically,in preparing these exemplified formulations, the flavor is first addedto the carrier liquid, e.g. ethanol, with agitation. The component Esurfactants, where used, are then slowly sprinkled in with constantstirring, after which sufficient water is added slowly with stirring forabout ten minutes or until all the surfactants are dissolved and thesolution is clear. The component D polyhydric alcohol, if used, is thenadded slowly with stirring followed by addition of the optionalcomponent F sweetener, preferably previously solubilized in a littlewater. Coloring agent, hydrogen peroxide (in the form of a 35% aqueoussolution), and the remainder of the water are then added in succession.

The pastes and gels may be prepared from the formulation liquids merelyby adding the thickener and/or gelling agent and if necessary theperoxygen source to bring it up to specifications in the final formula.Alternatively, all of the ingredients are added as above for solutionpreparation except before adding the peroxide, the gelling agent and orthickener in aliquot portion of water is added followed by the peroxide.In this procedure one may also add the flavors after the thickenerrather than at the onset.

                  TABLE 1                                                         ______________________________________                                               Examples (% w/v)                                                              1      2        3      4     5     6                                   ______________________________________                                        Ethanol.sup.1                                                                          4.75     4.75     4.75 4.75  4.75  4.75                              Wintergeen                                                                             0.22     0.22     0.22             0.22                              Flavor.sup.2                                                                  Cinnamon                        0.15  0.15                                    Flavor.sup.3                                                                  Pluronic 1.0      1.0      1.0  1.0   1.0   1.0                               F108                                                                          Polysorbate                                                                            0.6      0.6      0.6  0.6   0.6   0.6                               20.sup.4                                                                      Sorbitol.sup.5                                                                         10.5              10.5 10.5                                          Glycerin          5.0                 5.0   5.0                               Sodium   0.04     0.04     0.04 0.04  0.04  0.04                              saccharin                                                                     FD & C Blue                                                                            .0004    .0004                                                       No. 1.sup.6                                                                   FD & C Red                      .002  .002                                    No. 40.sup.6                                                                  Hydrogen 1.5      1.5      1.5  1.5   1.5   1.5                               peroxide.sup.7                                                                Purified ← qs. to 100 v. →                                        Water                                                                         (USP Deion-                                                                   ized)                                                                         ______________________________________                                         .sup.1 in form of 95% soln                                                    .sup.2 80% methyl salicylate, 20% menthol                                     .sup.3 7.5% menthol, 35% cinnamic aldehyde, 7.5% clove oil in propylene       glycol soln                                                                   .sup.4 Tween 20polyoxyethylene (20) sorbitan monolaurate                      .sup.5 in form of 70% soln                                                    .sup.6 in form of 1% soln                                                     .sup.7 in form of 35% soln                                               

All the above-exemplified formulations represent satisfactory, pleasing,acceptable and effective foaming oxygenating mouthrinses havingsatisfactory storage stability with respect to flavor, color,appearance, taste, peroxy content and the like.

The foregoing examples are repeated except 18% of Pluronic F127 gellingagent is provided in formulations and in each instance good, "ringing"gel is produced. The gelling agent is mixed with a major amount (90%) ofthe formula water & polyhydric alcohol to which is added the alcohol,flavor and surfactant (F108 and polysorbate) mixture and finally thesaccharin, colorant (s) and hydrogen peroxide. The temperature isgenerally maintained at around 0° C. (e.g. -5 to 10° C.) duringpreparation of water-gelling agent mixture and also during addition ofother ingredients to this mixture. These examples are 1a to 6a.

EXAMPLE 7

75 grams of a 70% aqueous solution of sorbitol, 2.0 mg. of Blue Dye #1and 470 ml of water are mixed and cooled to 5° C. To the mixture firstthere is added 125 grams of Pluronic F127 and after dissolution thereofthere are added 1.1 grams of Wintergreen Flavor (as in Examples 1-6) and21.4 grams of 35% aqueous hydrogen peroxide (USP). The mixture isallowed to come to room temperature. The next day it is noted that agood gel has formed. The amount of gelling agent (i.e. Pluronic F127) isabout 18% by weight.

EXAMPLE 8

Example 7 is repeated except that along with initial mixture ofsorbitol, dye and water there is added 5 grams of Carbopol 934 (acarboxylated vinyl polymer). The resultant product after a few days is a"heavy syrup".

EXAMPLE 9

25 grams of 95% USP ethanol and 0.85 grams of Wintergreen flavor (0.68g. methyl salicylate and 0.17 g. USP menthol) are mixed. To this isadded 3.85 g. of Pluronic F108 and mixing is done for 20 minutes. Then1.25 g. of water are added with mixing. 2.3 g. of Polysorbate 20 N.F.(non-ionic) is added and mixed for 10 minutes. To 2.85 g. of water areadded 60 g. of 70% aqueous sorbitol (USP) and the temperature lowered to0°-5° C. To this cold solution are added 100 g. of Pluronic F127. It isnoted that temperature drops to -2° C. Mixing is done for 40 minutes. Tothis cold mixture is added the alcohol, flavor, Pluronic F108, andPolysorbate mixture. Then 0.15 g. of sodium saccharin (USP), 0.0015 g.FD & C Blue #1, and 21.43 g. of 35% aqueous hydrogen peroxide are addedand well mixed for about 10 minutes. Excellent gel is formed.

This invention has been disclosed with respect to preferred embodiments,and various modications and variations thereof obvious to those skilledin the art are to be included within the spirit and purview of thisapplication and the scope of the appended claims.

We claim:
 1. An aqueous oral composition comprising:(a) from about 0.5to about 5% by weight of hydrogen peroxide, and (b) a flavoring agentselected from the group consisting of:(1) wintergreen flavor containingmethyl salicylate and menthol in a weight ratio of about 3:1 to 5:1, and(2) cinnamon flavor containing 6-9% menthol, 32-38% cinnamic aldehydeand 6-9% clove oil
 2. An oral composition according to claim 1 includingfrom about 3 to 10% by weight of ethanol.
 3. An oral compositionaccording to claim 1 including from about 1 to 20% by weight ofpolyhydric alcohol.
 4. An oral composition according to claim 1including from about 0.1% to about 10% non-ionic surfactant.
 5. An oralcomposition according to claim 1 wherein the amount of hydrogen peroxideis from about 1% to about 3%, and including about 0.5 to 5% non-ionicsurfactant, about 3-10% ethanol and about 3-15% polyhydric alcoholselected from glycerol and sorbitol.
 6. An oral composition according toclaim 5 wherein the non-ionic surfactant comprises from about 0.5% to 3%of a water soluble polyoxyethylenated-polyoxypropylene polyol and fromabout 0.3% to 2% of a water soluble polyoxyethylenated monoester ofsorbitol with a C₁₀ to C₁₈ fatty acid.
 7. A mouthrinse solutioncomprising the oral composition of claim
 1. 8. An aqueous oral gelcomprising the oral composition of claim
 1. 9. An aqueous oral gelaccording to claim 8 including from about 1% to about 50% of a gellingagent.
 10. An aqueous oral gel according to claim 9 wherein the amountof gelling agent is from about 5% to 30% by weight of the gel.
 11. Anaqueous oral gel according to claim 10 wherein the gelling agent is awater-soluble carboxymethylcellulose.
 12. An aqueous oral gel accordingto claim 11 wherein the gelling agent is sodium carboxymethylcellulose.13. An aqueous oral gel according to claim 10 wherein the gelling agentis a polyoxyethylenated-polyoxypropylene polyol wherein thepolyoxypropylene hydrophobic moiety has a molecular weight of about 3500to 4000 and the hydrophilic polyoxyethylene content constitutes about 30to 80% of the molecule.